MedDRA Important Medical Events (IME) in the EU Patricia Mozzicato, MD MedDRA MSSO
Topics Covered MedDRA refresher Background of IME list Considerations in maintaining MedDRAbased term lists Inclusion/exclusion criteria Version updates Examples from draft IME list IME list survey 2
MedDRA Refresher Drug Information Association www.diahome.org 3
MedDRA Definition MedDRA is a clinically-validated international medical terminology used by regulatory authorities and the regulated biopharmaceutical industry. The terminology is used through the entire regulatory process, from pre-marketing to post-marketing, and for data entry, retrieval, evaluation, and presentation. 4
Regulatory Status of MedDRA in EU Clinical trials SUSARs (Suspected Unexpected Serious Adverse Reactions) Volume 9A Individual Case Safety Reports (ICSRs) Adverse reactions in PSUR Standardised MedDRA Queries (SMQs) recommended for signal detection Interface between EudraVigilance and EU Risk Management Plan indications, risks, interactions Summary of Product Characteristics guideline 5
Scope of MedDRA 6
MedDRA s Structure 7
Multi-Axiality SOC = Respiratory, thoracic and mediastinal disorders SOC = Infections and infestations HLGT = Respiratory tract infections HLGT = Viral infectious disorders HLT = Viral upper respiratory tract infections HLT = Influenza viral infections PT = Influenza 8
Multi-Axiality (cont) For multi-axial terms, one SOC is primary Primary SOC rules for: SOC Congenital, familial and genetic disorders SOC Infections and infestations SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) Three SOCs are not multi-axial: SOC Investigations SOC Social circumstances SOC Surgical and medical procedures 9
MedDRA and the MSSO International support and development of terminology Foster use of MedDRA through communications and educational offerings Custodians, not owners, of the terminology JMO (partner organization for Japaneselanguage MedDRA) Governed by a Management Board (industry, regulators, multi-national, other interested parties) 10
Background of IME List Drug Information Association www.diahome.org 11
Purpose of IME List Facilitate: Classification of suspected adverse reactions Aggregate data analysis Case assessment for pharmacovigilance activities Intended for guidance purposes only Not mandatory requirement for regulatory reporting Option to use it for other purposes 12
Initial Development of IME List Development by EV-EWG started in May 2007 Identified MedDRA Preferred Terms (PTs) that are medically important regardless of presence of other regulatory seriousness criteria Based on an MHRA list 13
Initial Development of IME List (cont) All terms in three SOCs initially INCLUDED: SOC Congenital, familial and genetic disorders SOC Infections and infestations SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) All terms in two SOCs initially EXCLUDED: SOC Social circumstances SOC Surgical and medical procedures Remaining terms in 21 SOCs were assessed by volunteers with medical background 14
Inclusion of PTs on IME List Divided terms for inclusion into: Core serious (CS) always serious Extended serious (ES) serious in some circumstances only Teams of 4 6 volunteers reviewed the terms: If majority agreed, term added If tie, the more conservative assessment was taken (e.g., if 3 for CS and 3 for ES, term became CS) 15
Maintaining MedDRA-based Term Lists Drug Information Association www.diahome.org 16
MSSO and MedDRA Term Lists Term lists maintained by MedDRA MSSO Gender-Specific Adverse Events Pediatric Adverse events Standardised MedDRA Queries (SMQs) 17
Considerations for Maintaining Term Lists Understand purpose of list What is the intended use of the list? Are there other ways the list may be used? Understand scope of list What are the inclusion/exclusion criteria? 18
Maintenance of IME List List received for review in MedDRA v12.0; approx. 9000 PTs To update list to MedDRA v12.1, first inclusion/exclusion criteria needed to be developed Draft incl/excl criteria: Overall SOC-specific 19
Maintenance of IME List (cont) Inclusion/exclusion criteria based on ICH definition of an IME may not be immediately lifethreatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above. 20
Examples: Inclusion/Exclusion Criteria Overall Included Generally, all infarct/infarction terms (e.g., PT Renal infarct) Terms for failure or insufficiency of lifesustaining organ systems (PT Hepatic failure) Excluded Pain and discomfort terms (PT Pain of skin) 21
Examples: Inclusion/Exclusion Criteria (cont) SOC Cardiac disorders: Included All terms for cardiac valve disorders (e.g., PT Aortic valve stenosis) All terms for endocardial disorders (PT Endocardial fibrosis) Excluded Terms for trivial arrhythmias that do not lead to more significant consequences (PT Extrasystoles) 22
Development of CS/ES Criteria Core serious Precisely fits definition of an IME Example: PT Stroke in evolution Extended serious Does not precisely fit definition Sometimes rather broad concept With additional clinical information, may be or evolve into an IME Example: PT Anaemia 23
Maintenance of IME List Original scope of IME list changed Selected (not all) PTs from these SOCs are included: SOC Congenital, familial and genetic disorders SOC Infections and infestations SOC Neoplasms benign, malignant and unspecified (incl cysts and polyps) Selected PTs from these SOCs are included (had originally been excluded): SOC Social circumstances SOC Surgical and medical procedures 24
Maintenance of IME List (cont) Apply incl/excl criteria to new v12.1 PTs Review existing terms on list against new criteria Review terms not on list against new criteria Check for other PT changes (demotion to LLT, change of primary SOC) 25
Versioning of IME List EV-EWG and PhVWP have both reviewed revised term list and proposed inclusion/exclusion criteria List will be updated with each new MedDRA version Experts will review updated lists and criteria with each new version 26
Current Activities EV-EWG created a survey for those who downloaded IME list Survey will be available online until 26 October 2010 (EudraVigilance Web site, under News - http://eudravigilance.emea.europa.eu/human/ index.asp) Takes about 15-20 mins to complete Data will be treated in a confidential way: summary will be shared with MSSO, MedDRA Management Board and other interested parties 27
Goals of Survey To assess: Type of users who tested the IME list How IME list has been tested How useful IME list has been How to improve IME list in the future 28
Thank you Drug Information Association www.diahome.org 29